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基于谷胱甘肽和 pH 值比率检测的纳米级金属有机层对线粒体失调和化疗耐药性的检测

Nanoscale Metal-Organic Layers Detect Mitochondrial Dysregulation and Chemoresistance via Ratiometric Sensing of Glutathione and pH.

机构信息

Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province and State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.

出版信息

J Am Chem Soc. 2021 Jan 27;143(3):1284-1289. doi: 10.1021/jacs.0c11764. Epub 2021 Jan 15.

Abstract

Mitochondrial dysregulation controls cell death and survival by changing endogenous molecule concentrations and ion flows across the membrane. Here, we report the design of a triply emissive nanoscale metal-organic layer (nMOL), NA@Zr-BTB/F/R, for sensing mitochondrial dysregulation. Zr-BTB nMOL containing Zr secondary building units (SBUs) and 2,4,6-tris(4-carboxyphenyl)aniline (BTB-NH) ligands was postsynthetically functionalized to afford NA@Zr-BTB/F/R by exchanging formate capping groups on the SBUs with glutathione(GSH)-selective (2)-1-(2'-naphthyl)-3-(4-carboxyphenyl)-2-propen-1-one (NA) and covalent conjugation of pH-sensitive fluorescein (F) and GSH/pH-independent rhodamine-B (R) to the BTB-NH ligands. Cell imaging demonstrated NA@Zr-BTB/F/R as a ratiometric sensor for mitochondrial dysregulation and chemotherapy resistance via GSH and pH sensing.

摘要

线粒体失调通过改变膜内内源性分子浓度和离子流来控制细胞的死亡和存活。在这里,我们报告了一种三重发光纳米级金属有机层(nMOL),即 NA@Zr-BTB/F/R,用于感测线粒体失调。含有 Zr 次级结构单元(SBUs)和 2,4,6-三(4-羧基苯基)苯胺(BTB-NH)配体的 Zr-BTB nMOL 通过用谷胱甘肽(GSH)选择性(2)-1-(2'-萘基)-3-(4-羧基苯基)-2-丙烯-1-酮(NA)交换 SBU 上的甲酸盐封端基团,以及共价连接 pH 敏感的荧光素(F)和 GSH/pH 独立的若丹明 B(R)到 BTB-NH 配体上,从而被后合成功能化得到 NA@Zr-BTB/F/R。细胞成像表明,NA@Zr-BTB/F/R 可以作为一种通过 GSH 和 pH 感测来检测线粒体失调和化疗耐药性的比率型传感器。

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Mitochondria as multifaceted regulators of cell death.线粒体作为细胞死亡的多面调节者。
Nat Rev Mol Cell Biol. 2020 Feb;21(2):85-100. doi: 10.1038/s41580-019-0173-8. Epub 2019 Oct 21.
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Mitochondria and Cancer.线粒体与癌症
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